Cardiovascular effects of IV administered ketamine (10 mg/kg) and midazolam (0.5 mg/kg) were determined in 12 healthy isoflurane-anesthetized (1.7% end-tidal concentration) dogs. Six dogs received a ketamine-midazolam combination (K-M) as a bolus over 30 seconds and 6 dogs received K-M as an infusion over 15 minutes. Ketamine-midazolam combination as a bolus and an infusion caused early significant (P < 0.05) reductions in mean systemic blood pressure, cardiac index, and stroke index, which returned to baseline values near the end of the study. Heart rate decreased significantly (P < 0.05) in dogs of the infusion group and returned to the baseline value near the end of the study. One dog died after K-M bolus administration. Mean maximal decreases from baseline for systemic blood pressure, cardiac index, and stroke index were significantly (P < 0.05) greater in dogs of the bolus group than in dogs of the infusion group; therefore, cardiovascular effects of K-M after infusion were less severe than those after bolus. Base excess and pHa decreased significantly (P < 0.05) in the infusion group, although similar changes occurred in both groups. Four dogs were maintained with 1.7% end-tidal isoflurane to determine temporal effects of isoflurane; these dogs did not receive K-M. Increases in heart rate, cardiac index, stroke index, and left and right ventricular stroke work indexes were significant (P < 0.05) at various sample collection intervals, particularly during the later stages of the study. Isoflurane anesthesia effectively blocked the cardiostimulatory properties of K-M. Ketamine-midazolam combination should be used cautiously during isoflurane anesthesia, and administration by slow infusion may be safer than by rapid bolus administration.